Focal adhesions contain three specialized actin nanoscale layers
Reena Kumari,
Katharina Ven,
Megan Chastney,
Shrikant B. Kokate,
Johan Peränen,
Jesse Aaron,
Konstantin Kogan,
Leonardo Almeida-Souza,
Elena Kremneva,
Renaud Poincloux,
Teng-Leong Chew,
Peter W. Gunning,
Johanna Ivaska and
Pekka Lappalainen ()
Additional contact information
Reena Kumari: University of Helsinki
Katharina Ven: University of Helsinki
Megan Chastney: University of Turku and Åbo Akademi University
Shrikant B. Kokate: University of Helsinki
Johan Peränen: University of Helsinki
Jesse Aaron: HHMI Janelia Research Campus
Konstantin Kogan: University of Helsinki
Leonardo Almeida-Souza: University of Helsinki
Elena Kremneva: University of Helsinki
Renaud Poincloux: Université de Toulouse, CNRS, UPS
Teng-Leong Chew: HHMI Janelia Research Campus
Peter W. Gunning: UNSW Sydney, Wallace Wurth Building
Johanna Ivaska: University of Turku and Åbo Akademi University
Pekka Lappalainen: University of Helsinki
Nature Communications, 2024, vol. 15, issue 1, 1-20
Abstract:
Abstract Focal adhesions (FAs) connect inner workings of cell to the extracellular matrix to control cell adhesion, migration and mechanosensing. Previous studies demonstrated that FAs contain three vertical layers, which connect extracellular matrix to the cytoskeleton. By using super-resolution iPALM microscopy, we identify two additional nanoscale layers within FAs, specified by actin filaments bound to tropomyosin isoforms Tpm1.6 and Tpm3.2. The Tpm1.6-actin filaments, beneath the previously identified α-actinin cross-linked actin filaments, appear critical for adhesion maturation and controlled cell motility, whereas the adjacent Tpm3.2-actin filament layer beneath seems to facilitate adhesion disassembly. Mechanistically, Tpm3.2 stabilizes ACF-7/MACF1 and KANK-family proteins at adhesions, and hence targets microtubule plus-ends to FAs to catalyse their disassembly. Tpm3.2 depletion leads to disorganized microtubule network, abnormally stable FAs, and defects in tail retraction during migration. Thus, FAs are composed of distinct actin filament layers, and each may have specific roles in coupling adhesions to the cytoskeleton, or in controlling adhesion dynamics.
Date: 2024
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DOI: 10.1038/s41467-024-46868-7
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